1. Field of the Invention
The present invention relates to a new biomaterial, called a composite membrane, formed from hyaluronic acid derivatives, processes for its production, and the use of such composite membranes in surgery for the guided regeneration of tissues in the treatment of superficial and internal lesions.
2. Description of Related Art
Hyaluronic acid is a natural heteropolysaccharide composed of alternating residues of D-glucuronic acid and N-acetyl-D-glucosamine. It is a linear polymer with a molecular weight of between 50,000 and 13,000,000 depending upon the source from which it is obtained, and the preparation and determination methods employed. It is present in nature in pericellular gels, in the fundamental substance of connective tissues of vertebrate organisms of which it is one of the main components, in the synovial fluid of joints, in the vitreous humor, in human umbilical cord tissues, and in cocks' combs.
There are known, specific fractions of hyaluronic acid with definite molecular weights that do not present inflammatory activity and which can therefore be used to facilitate wound healing, or to substitute for the endobulbar fluids, or which can be used in therapy for joint pathologies by intra-articular injections as described in European Patent No. 0 138 572 granted to Applicants on Jul. 25, 1990.
Also known are hyaluronic acid esters, wherein all or some of the carboxy groups of the acid are esterified, their use in the pharmaceutical and cosmetic fields and in the area of biodegradable plastic materials, as described in U.S. Pat. Nos. 4,851,521, 4,965,353, and 5,147,861 granted to Applicants, and in European Patent Application 0 251 905 A2, published on Jan. 7, 1988.
Hyaluronic acid is known to play a fundamental role in tissue repair processes, especially in the first stages of granulation, by stabilizing the coagulation matrix and controlling its degradation, favoring the recruitment of inflammatory cells such as polymorphonuclear leukocytes and monocytes, of mesenchymal cells such as fibroblasts and the endothelial cells, and orienting the subsequent migration of epithelial cells.
It is known that the application of solutions of hyaluronic acid can accelerate healing in patients affected by bedsores, wounds and burns.
The role of hyaluronic acid in the various phases that constitute tissue repair processes have been described, by the construction of a theoretical model, by Weigel P. H. et al.: "A model for the role of hyaluronic acid and fibrin in the early events during the inflammatory response and wound healing," J. Theor. Biol., 119: 219, 1986.
Studies aimed at obtaining manufactured products to apply to the skin, composed of hyaluronic acid esters as such or in mixtures with other polymers, have led to the creation of various types of products. Among these are tissues, such as gauzes of varying thickness (number of threads per centimeter), with varying dimensions and with threads of varying denier (weight per 9000 meters of thread).
Films of widely varying thickness have been proposed as described in U.S. Pat. Nos. 4,851,521 and 4,965,353.
One of the limitations to the use of manufactured products composed of hyaluronic acid esters or mixtures of the same with other polymers is their low mechanical resistance, which may cause various problems with their use. In the case of biomaterials, such as membranes or other types of film-forming products, that have to be sewn in place, surgical needles or suture threads can give rise to cracks, cuts or lacerations that jeopardize the structural soundness of the membrane, and consequently the stability of the membrane in its place of application, thus laying the wound open to contamination and undesirable consequences.
Modern surgery now tends to employ, wherever possible, biomaterials with high biocompatibility, such as those obtained from hyaluronic acid esters, characterized also by high biodegradability and bioabsorbability.